Overall, up to 130 patients were planned to be enrolled in the study. In Part 1,
approximately 40 patients were planned to be enrolled, assuming 9 to 10 cohorts. Part 1
was open-label, and no randomization or blinding was required. In Part 2A, approximately
45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/m2)
and topotecan (0.75 mg/m2) or placebo and topotecan (1.5 mg/m2). In Part 2B,
approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib
(240 mg/mg2) and topotecan (1.5 mg/m2) or placebo and topotecan (1.5 mg/m2).
Patients who received placebo in Part 2A and Part 2B were to be combined into a single
placebo group for the analysis to compare with trilaciclib+topotecan 1.5 mg/m2 with
placebo + topotecan 1.5 mg/m2 (proximately 30 per treatment group).
The sample size calculation was to demonstrate the superiority of trilaciclib + topotecan
1.5 mg/m2 over placebo + topotecan 1.5 mg/m2 with respect to at least 1 of the primary
endpoints. The overall type I error rate was 1-sided 0.10. Using the most conservative
Bonferroni procedure for the 2 primary endpoints, a 1-sided individual type I error rate
0.10/2=0.05 was assigned to each outcome variable (DSN in Cycle 1 and occurrence of SN)
in the sample size calculation. Assuming a common standard deviation of 2.5, a difference
in the duration of SN in Cycle 1 of at least 2 days between the treatment groups, a
sample size of 28 per arm was required to have 90% power to detect the assumed treatment
effect. For occurrence of SN, assuming the event rate was 45% for placebo group, to
detect an absolute reduction of 37% by trilaciclib group with 90% power would require a
sample size of at least 29 per arm. Thus, 30 per arm was needed to ensure 90% power to
detect assumed treatment effect for DSN in Cycle 1 and occurrence of SN. All calculations
were carried out using the POWER procedure in SAS®, Version 9.4 procedure in SAS®,
Version 9.4 or higher.
The results from endpoints that were commonly collected at Part 1 and part 2 are
presented together in this report.
The posted results represent the final results of Study G1T28-03, a Phase 1b/2a safety
and pharmacokinetic (PK) study of trilaciclib (G1T28) in patients with previously treated
extensive-stage small cell lung cancer (SCLC) receiving topotecan chemotherapy in the
second/third-line (2/3L) setting. The final myelopreservation efficacy results for both
parts and exposure for Part 1 are from database lock 1 (data cut-off [DCO] for Primary
Completion Date [PCD] 28 September 2018). The final anti-tumor efficacy (BOR, DOR, PFS)
for both parts, final overall survival for Part 1 and exposure data from Part 2 are from
a second database lock 2 (DCO 31 May 2019) and the final overall survival for Part 2 and
safety (adverse events) are through the end of the study on October 4, 2021 which
resulted in the final database lock (DCO 01 Nov 2021).
The maximum time frames provided reflect the time from when the first patient could be
evaluated for an endpoint (ie. date of first dose of first patient) to the time when the
data from both parts presented for that endpoint was considered final.
